Calcium supplements are widely used for the treatment of osteoporosis. The bioavailability of these preparations are relatively low. This problem has been noted by a number of medical professionals recently as the issue of osteroporosis in an aging population is becoming a well publicized issue (F-D-C-Reports--"The Tan Sheet", Mar. 14, 1994). Not all calcium supplements are the same. Bioavailability appears to differ among and between sources of calcium. It often is influenced by manufacturing processes. Solubility in vitro is not necessarily correlated with bioavailability. And even though the same total amount of calcium is ingested, more calcium may be absorbed if the supplement is taken in multiple small doses, especially when taken with food, that when taken in just a few large doses. Other nutritional depravations, such as inadequate vitamin D intake, may influence calcium absorption. What ever the reason, calcium absorption from supplements can be quite variable from preparation to preparation and is not a particularly efficient process vis-a-vis the currently available oral supplements.
Adequate calcium intake whether from food or supplements is important in both preventive and treatment regimens for osteoporosis and osteomalacia. The use of calcium supplements has increased dramatically in recent years. Some recent evidence indicates that calcium intake may be associated with a reduced risk of colon cancer and may have a blood-pressure lowering effect. If these initial results are verified it will likely further increase the use of calcium supplements, making it more important that optimal dosing regimens be developed to minimize toxicity and maximize their efficacy (J. Blanchard and J. M. Aeschlimann. Calcium Absorption in Man: Some Dosing Recommendations. J. Pharmacokinetics and Biopharmaceutics, 17(6), 1989, 631-644). Concern has been expressed that the bioavailability of calcium from many calcium carbonate supplements is low. For most commercially available products, calcium absorption in adults commonly averages 25-35% of the available calcium in the dosage form. The low bioavailability could be attributed to either an incomplete drug release or to a too short residence time of the pharmaceutical dosage form in the absorption section of the GI Tract (H. M. Ingani, et al. Conception and in vivo investigation of peroral sustained release floating dosage forms with enhanced gastrointestinal transit. Int. J. Pharm., 35 (1987) 157-164). Therefore, design of better delivery systems seem to be necessary. Some researchers have shown that the absorption of calcium involves a saturable (active) and a nonsaturable (passive) component. The combination of the acidic pH and calcium binding protein in the duodenum and upper jejunum makes the absorption of calcium much greater in the duodenojejunal section (Lindsay H. Allen. Calcium bioavailability and absorption: a review. Am J Clin Nutr., 1982; 35;783-808). The work of several other investigators indicate that an inverse relationship exists between calcium intake and absorption efficiency. The division of the daily dose into equal increments taken at equally spaced interval over the course of the day is recommended as a useful procedure for increasing the absorption efficiency and efficacy. In addition, it is reported that single unit systems can be retained in the stomach for long periods (10 hours and longer) if administered after a heavy meal (R. Malagelada et al. The stomach, but not small bowel, discriminates between solid and liquids in man. Gastroenterology, 84 (1983) 1237).
Previous studies aimed at increasing calcium uptake in the intestine have mainly concentrated on increasing the dissolution rate and increasing the solubility of the calcium source. Based on this information, controlled release calcium oral dosage forms with increased gastric retention time seem to be appropriate to increase the bioavailability.
To achieve this goal a hydrophilic matrix system was used to encapsulate a source of calcium ion, such as for example calcium carbonate. The test matrix material was different grades of hydroxypropylmethylcellulose (HPMC). The grades of HPMC represent a variety of polymers with different molecular weights. Methocel K100LV and K4M were selected. It is reported that these polymers demonstrate floating and swelling behavior. V. S. Gerogiannis, et al., Floating and swelling characteristics of various excipients used in controlled release technology, Drug Dev. Ind. Pharm., 19(9), 1061-1081 (1993)!.